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中国药学(英文版) ›› 2025, Vol. 34 ›› Issue (9): 821-830.DOI: 10.5246/jcps.2025.09.060

• 【研究论文】 • 上一篇    下一篇

纳米颗粒氢氧化铝佐剂室温储存过程中质量稳定性研究

杨希飞, 张飞伟*()   

  1. 成都生物制品研究所有限责任公司 细菌性疫苗一室, 四川 成都 610023
  • 收稿日期:2025-03-15 修回日期:2025-04-10 接受日期:2025-04-23 出版日期:2025-10-02 发布日期:2025-10-02
  • 通讯作者: 张飞伟

Stability of aluminum hydroxide nanoparticle adjuvants during room temperature storage

Xifei Yang, Feiwei Zhang*()   

  1. Bacterial Vaccine Room 1, Chengdu Institute of Biological Products Co., Ltd., Chengdu 610023, Sichuan, China
  • Received:2025-03-15 Revised:2025-04-10 Accepted:2025-04-23 Online:2025-10-02 Published:2025-10-02
  • Contact: Feiwei Zhang

摘要:

氢氧化铝佐剂为弱结晶勃姆石(PCB)结构,储存过程中不稳定。本研究通过考察佐剂晶体结构、粒径分布、电镜结构、pH值、等电点和吸附速率等质量指标, 全面揭示佐剂在室温储存过程中质量变化, 以保证疫苗安全有效生产。将3批氢氧化铝佐剂在室温条件下储存15个月, 检测X-射线衍射图、透射电子显微镜结构图、pH值、等电点(pI)和吸附能力的变化情况。X-射线衍射图显示氢氧化铝佐剂晶体结构最初为PCB, 在室温储存过程中晶体结构有序性增加。在储存至12个月时, 衍射图在18.2° 2θ出现新的衍射峰, 且衍射峰的强度随储存时间增加而加强, 伴随高结晶的三水铝石及拜耳石产生, 不利于佐剂质量稳定性。此外, 储存期间佐剂pH和pI降低, 化学稳定性下降。该佐剂是由平均粒径为130 nm的初级粒子组成, 具有比表面积大和吸附能力强的特点。因此, 佐剂对牛血清白蛋白(BSA)具有较高的吸附能力, 约为8 mg BSA/mg Al3+, 储存至15个月与第1个月相比吸附能力无明显变化 (P > 0.05)。这表明纳米颗粒氢氧化铝佐剂在整个储存过程中保持着较高的吸附效率, 使其成为一种有效的疫苗吸附剂。然而, 在储存后期, 出现了高结晶的三水铝石及拜耳石, 同时伴随pH和等电点下降, 不利于佐剂的质量稳定性。基于以上研究结果, 建议纳米颗粒氢氧化铝佐剂的有效期不应超过12个月, 以保证其质量稳定性和有效性。

关键词: 纳米颗粒, 氢氧化铝佐剂, X射线衍射图, 弱结晶勃姆石, 等电点, 透射电子显微镜, 吸附能力

Abstract:

Aluminum hydroxide adjuvant exhibits a poorly crystalline boehmite (PCB) structure, which demonstrates instability during prolonged storage. In the present study, we systematically investigated the quality alterations of the adjuvant stored at room temperature by analyzing its crystal structure, particle size distribution, electron microscopic characteristics, pH, isoelectric point (pI), and adsorption capacity. These assessments aimed to ensure the effectiveness and safety of vaccine production. Three batches of adjuvants were stored at room temperature for 15 months, and their changes were monitored using X-ray diffraction patterns, transmission electron microscopy (TEM), pH measurements, pI determination, and adsorption capacity analysis. X-ray diffraction revealed that the crystalline phases of aluminum hydroxide initially exhibited a PCB structure, which became progressively more ordered during storage. Notably, after 12 months, a new diffraction peak emerged at 18.2° 2θ, with its intensity increasing over time. This corresponded to the formation of highly crystalline gibbsite and bayerite, which compromised the stability of the adjuvant. Furthermore, the pH and pI values decreased during storage, reflecting a decline in the chemical stability of the adjuvant. Comprising nanoparticles with a mean diameter of 130 nm, the adjuvant maintained a high surface area and excellent adsorption capacity. The adsorption rate at 8 mg BSA/mg Al3+ consistently exceeded 97%, with no statistically significant differences observed between the adsorption capacities at 1 and 15 months (P > 0.05). This indicated that the nanoparticle aluminum hydroxide adjuvant sustained high adsorption efficiency throughout the storage period, underscoring its reliability as a vaccine adsorbent. However, in the later stages of storage, the emergence of highly crystalline gibbsite and bayerite, coupled with declines in pH and pI, negatively impacted the adjuvant’s stability. Based on these findings, we recommended that aluminum hydroxide adjuvants should not be stored at room temperature for longer than 12 months to preserve their quality and efficacy.

Key words: Nanoparticles, Aluminum hydroxide adjuvant, X-ray diffraction pattern, Poorly crystalline boehmite, Isoelectric point, Transmission electron microscopy, Adsorption capacity

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